Vascular inducing implants

ABSTRACT

Implants and associated delivery systems for promoting angiogenesis in ischemic tissue are provided. The implants may be delivered percutaneously, thoracically or surgically and are particularly well suited for implantation into the myocardium of the heart. The implants are configured to have a first configuration having a low profile and an expanded, second configuration having a large profile. The implants are delivered to the ischemic tissue location in the first configuration, implanted then expanded to the second configuration. The expanded implants maintain a stress on the surrounding tissue, irritating and slightly injuring the tissue to provoke an injury response that results in angiogenesis. The flow of blood from the surrounding tissue into the implant and pooling of the blood in and around the implant leads to thrombosis and fibrin growth. This healing process leads to angiogenesis in the tissue surrounding the implant. Additionally, the implants may contain an angiogenic substance or a thrombus of blood, preloaded or injected after implantation to aid in initiating angiogenesis.

FIELD OF THE INVENTION

[0001] This invention relates to methods and devices for inducingangiogenesis in ischemic tissue.

BACKGROUND OF THE INVENTION

[0002] Tissue becomes ischemic when it is deprived of oxygenated blood.Blood may be present in such tissue, though it is not carrying oxygen.Ischemic tissue can be revived to function normally if it has remainedviable despite the deprivation of oxygenated blood. Ischemia can becaused by a blockage in the vascular system that prohibits oxygenatedblood from reaching the affected tissue area. Ischemia causes pain inthe area of the affected tissue and in the case of muscle tissue caninterrupt muscular function.

[0003] Although ischemia can occur in various regions of the body, oftentissue of the heart, the myocardium, is affected by ischemia due tocoronary artery disease, occlusion of the coronary artery, whichotherwise provides blood to the myocardium. Muscle tissue affected byischemia can cause pain to the individual affected. Ischemia can betreated, if a tissue has remained viable despite the deprivation ofoxygenated blood, by restoring blood flow to the affected tissue.

[0004] Treatment of myocardial ischemia has been addressed by severaltechniques designed to restore blood supply to the affected region.Coronary artery bypass grafting CABG involves grating a venous segmentbetween the aorta and the coronary artery to bypass the occluded portionof the artery. Once blood flow is redirected to the portion of thecoronary artery beyond the occlusion, the supply of oxygenated blood isrestored to the area of ischemic tissue.

[0005] Early researchers, more than thirty years ago, reported promisingresults for revascularizing the myocardium by piercing the muscle tocreate multiple channels for blood flow. Sen, P. K. et al.,“Transmyocardial Acupuncture—A New Approach to MyocardialRevascularization”, Journal of Thoracic and Cardiovascular Surgery, Vol.50, No. 2, August 1965, pp. 181-189. Although others have reportedvarying degrees of success with various methods of piercing themyocardium to restore blood flow to the muscle, many have faced commonproblems such as closure of the created channels. Various techniques ofperforating the muscle tissue to avoid closure have been reported byresearchers. These techniques include piercing with a solid sharp tipwire, hypodermic tube and physically stretching the channel after itsformation. Reportedly, many of these methods still produced trauma andtearing of the tissue that ultimately led to closure of the channel.

[0006] An alternative method of creating channels that potentiallyavoids the problem of closure involves the use of laser technology.Researchers have reported success in maintaining patent channels in themyocardium by forming the channels with the heat energy of a laser.Mirhoseini, M. et al., “Revascularization of the Heart by Laser”,Journal of Microsurgery, Vol. 2, No. 4, June 1981, pp. 253-260. Thelaser was said to form channels in the tissue that were clean and madewithout tearing and trauma, suggesting that scarring does not occur andthe channels are less likely to experience the closure that results fromhealing. Aita U.S. Pat. Nos. 5,380,316 and 5,389,096 disclose anotherapproach to a catheter based laser system for TMR.

[0007] Although there has been some published recognition of thedesirability of performing transmyocardial revascularization (TMR) in anon-laser catheterization procedure, there does not appear to beevidence that such procedures have been put into practice. For example,U.S. Pat. No. 5,429,144 Wilk discloses inserting an expandable stentwithin a preformed channel created within the myocardium for thepurposes of creating blood flow into the tissue from the left ventriclePerforming TMR by placing stents in the myocardium is also disclosed inU.S. Pat. No. 5,810,836 (Hussein et al.). The Hussein patent disclosesseveral stent embodiments that are delivered through the epicardium ofthe heart, into the myocardium and positioned to be open to the leftventricle. The stents are intended to maintain an open a channel in themyocardium through which blood enters from the ventricle and perfusesinto the myocardium.

[0008] Angiogenesis, the growth of new blood vessels in tissue, has beenthe subject of increased study in recent years. Such blood vessel growthto provide new supplies of oxygenated blood to a region of tissue hasthe potential to remedy a variety of tissue and muscular ailments,particularly ischemia. Primarily, study has focused on perfectingangiogenic factors such as human growth factors produced from geneticengineering techniques. It has been reported that injection of such agrowth factor into myocardial tissue initiates angiogenesis at thatsite, which is exhibited by a new dense capillary network within thetissue. Schumacher et al., “Induction of Neo-Angiogenesis in IschemicMyocardium by Human Growth Factors”, Circulation, 1998; 97:645-650. Theauthors noted that such treatment could be an approach to management ofdiffused coronary heart disease after alternative methods ofadministration have been developed.

SUMMARY OF THE INVENTION

[0009] The vascular inducing implants of the present invention provide amechanism for initiating angiogenesis within ischemic tissue. Theimplants interact with the surrounding tissue in which they areimplanted and the blood that is present in the tissue to initiateangiogenesis by various mechanisms.

[0010] Primarily, it is expected that the implants will triggerangiogenesis in the ischemic tissue by interacting in one or more wayswith the tissue to initiate an injury response. The body's response totissue injury involves thrombosis formation at the site of the injury orirritation. Thrombosis leads to arterioles and fibrin growth which isbelieved to ultimately lead to new blood vessel growth to feed the newtissue with blood. The new blood vessels that develop in this regionalso serve to supply blood to the surrounding area of ischemic tissuethat was previously deprived of oxygenated blood.

[0011] The implant devices may be formed in a variety of configurationsto carry out the objectives outlined above for initiating angiogenesis.Specifically, the implants can be arranged in various ways to provide afirst configuration that presents a reduced profile and a secondconfiguration that is expanded to provide a larger profile that willirritate and place stress on the surrounding tissue into which it hasbeen implanted. The first configuration is suitable for delivery to thetissue site and into the tissue. The second configuration is obtainedafter the implant is placed in the tissue. Expansion of the device tothe larger profile configuration not only places stress on the tissuebut serves to rupture and injure the tissue slightly as it expands. Thechange in profile between the first configuration and secondconfiguration is of such a magnitude that the irritation and injurysuffered by surrounding tissue upon expansion of the implant will inducean injury response that results in angiogenesis. However, the magnitudeof the expansion to the second configuration is not so great that tissuebecomes severely injured: function impaired and unable to heal.

[0012] Additionally, each implant embodiment serves to provide aconstant source of irritation and injury to the tissue in which it isimplanted, thereby initiating the healing process in that tissue that isbelieved to lead to angiogenesis. As tissue surrounding the implantmoves, such as the contraction and relaxation of muscle tissue, somefriction and abrasion from the implant occurs, which injures the tissue.The injury caused by the outside surfaces of the implants to thesurrounding tissue does not substantially destroy the tissue, but issufficient to initiate an injury response and healing which leads toangiogenesis.

[0013] Implant embodiments of the invention also serve to initiateangiogenesis by providing an interior chamber into which blood mayenter, collect and thrombose. Blood that enters the implant and remains,even temporarily, tends to coagulate and thrombus. Over time, continuedpooling of the blood in the interior will cause thrombosis and fibringrowth throughout the interior of the implant and into the surroundingtissue. New blood vessels will grow to serve the new growth withoxygenated blood, the process of angiogenesis.

[0014] Implant embodiments may further be prepared to initiateangiogenesis by having a thrombus of blood associated with them at thetime of their implantation or inserted in the interior immediatelyfollowing implantation. The thrombus of blood may be taken from thepatient prior to the implant procedure and is believed to help initiatethe tissue's healing response which leads to angiogenesis.

[0015] Alternatively or in addition to a thrombus of blood, the implantdevices may be associated with an angiogenic substance in a variety ofways to aid the process of angiogenesis, In embodiments having a definedinterior, the substance may be placed within the interior prior toimplantation or injected after the implantation of the device. Thesubstance may be fluid or solid. The blood flow into and interactingwith the interior of the device will serve to distribute the substancethrough the surrounding tissue area because blood entering the devicemixes with and then carries away the substance as it leaves the device.Viscosity of the substance and opening size through which it passes,determine the time-release rate of the substance.

[0016] Substances may be associated with the device, not only by beingcarried within their interiors, but also by application of a coating tothe device. Alternatively, the substance may be dispersed in thecomposition of the device material. Alternatively, the implant may befabricated entirely of the angiogenic substance. Recognizing that thereare many ways to attach an angiogenic substance or drug to a device, themethods listed above are provided merely as examples and are notintended to limit the scope of the invention. Regardless of the methodof association, the implants of the present operation operate todistribute the angiogenic substance in surrounding tissue by theimplants contact with the tissue and blood supply in that tissue area.

[0017] By way of example, the implant device may comprise a helicalspring having a first configuration that is more tightly wound, havingan elongated length, more coils and a reduced diameter The secondconfiguration of the spring will provide an increased profile byincreasing the diameter of the coils through shortening the length ofthe spring.

[0018] In another embodiment, the implant may comprise a mesh tubecomprised of individual wire-like elements that are woven and arrangedto allow the tube to have a first configuration that is elongated with asmaller diameter and a second configuration that is shortened in length,but correspondingly larger in diameter and profile. In yet anotherconfiguration, the implant may comprise a sheet of solid or porousmaterial that is rolled into a tube. A first, reduced profileconfiguration of the tube is tightly rolled upon itself, storingpotential energy that will provide resilient expansion of the rolledtube to a less tightly rolled tubular shape when released. The expandedconfiguration of the tube provides a second configuration of the implantthat has a larger profile. In another embodiment, the implant maycomprise a spine having spaced along its length several C-shaped ringsthat may be compressed into a smaller profile in which the rings areclosed and a second configuration having an increased profile whereinthe rings are opened to a C-shape. The ends of the C-shaped rings may beformed to have eyelets that meet and are concentrically arranged whenthe rings are closed so that a release pin can be inserted through themto hold them in their reduced profile configuration. Once the implant isplaced within the tissue, the release pin may be removed permitting therings to resiliently expand to a C configuration.

[0019] In another embodiment, the implant may have a first configurationthat is uniaxial and a second configuration that is biaxial orbifurcated to provide an increased profile. The bifurcated embodimentsdisclosed may be comprised of single or double helical coils arranged tohave a trunk portion and two leg portions. The resulting appearance issimilar to a pair of pants. Alternatively, the bifurcated embodiment maybe configured as two spines having loops mounted concentrically alongtheir length, the spines being joined to several common loops at one endto form a trunk portion, and the other ends of the spine being free toform the leg portions of the implant. In both bifurcated implantembodiments, the loops or coils are interleaved while maintained in thefirst configuration such that they lie substantially along the sameaxis. In the second configuration, the spines spring apart to form aY-shaped or bifurcated configuration presenting a larger profile toincrease the injury to surrounding tissue and initiate angiogenesis.

[0020] Alternatively, the device may comprise a body that has attachedthereto flexible elements configured to retain, at least temporarily,blood or angiogenic substances. An example of such an embodiment wouldbe a small brush having an axial core member with a plurality offlexible bristles extending radially therefrom. The bristles having anatural resilience to a radially outward configuration with respect tothe core. During delivery of the brush into tissue, the bristles areswept back against the core. However, after insertion, the resilientbristles return at least partially to their radially outward extendingconfiguration, thereby placing surrounding tissue in stress and causingirritation to the tissue. The bristles are also configured to absorb, orhold within a hollow interior a drug or amount of quantity of blood.Additionally, the core member may be configured to define a hollowinterior capable of holding a therapeutic substance.

[0021] One or more implants of the present invention may be applied toan area of ischemic tissue. By way of example, the implants may define awidth of approximately 2 mm and a length corresponding to somewhat lessthan the thickness of the tissue into which it is implanted. It isanticipated that implants having a 2 mm wide profile would serve an areaof ischemic tissue of approximately one square centimeter to adequatelypromote angiogenesis throughout the surrounding region of tissue yetavoid altering the movement of the tissue due to a high density offoreign objects within a confined region of tissue.

[0022] The implants are delivered directly into the subject tissuewithout preforming a channel by removal of tissue such as by coring orablation by a laser. The delivery devices, while loaded with theimplant, operate to pierce and penetrate the tissue in a single drivingmotion. While the delivery device is penetrating the tissue, the implantis released and expanded into its second configuration within thetissue. The expanded implant is left behind as the delivery device iswithdrawn. Upon expansion of the device, the surrounding tissue may tearand become injured as it is pushed aside by the implant. The stressedtissue also tries to recoil around the device and may herniate throughopenings in the structure of the device. It is not important that theimplant maintain an open channel through the tissue for blood to flow.The objective of the implant is to trigger angiogenesis , so that newblood vessels will be created to introduce blood flow to the region.

[0023] The devices may be implanted percutaneously and transluminally,thoracically or surgically by a cut down method. In the case of implantsplaced within myocardial tissue of the heart, delivery systems aredisclosed for percutaneously accessing the left ventricle of the heartand penetrating and delivering the implant into the myocardium.

[0024] It is an object of the present invention to provide a method ofpromoting angiogenesis within ischemic tissue.

[0025] It is another object of the present invention to provide a methodof promoting angiogenesis by implanting a device within ischemic tissue.

[0026] It is another object of the present invention to provide a methodof promoting angiogenesis by causing thrombosis in the area of ischemictissue.

[0027] It is another object of the present invention to provide aprocess of promoting angiogenesis within ischemic myocardial tissue ofthe heart.

[0028] It is another object of the invention to provide an implantsuitable for implantation within tissue of the human body.

[0029] It is another objective of the present invention to provide animplant delivery system that is safe and simple to use while minimizingtrauma to the patient.

[0030] It is another object of the invention to provide an implant thatwill irritate tissue that surrounds the implant to initiate a healingresponse that leads to angiogenesis.

[0031] It is another object of the invention to provide an implanthaving a small profile first configuration and large profile secondconfiguration after implantation into tissue such that the implantplaces stress on the surrounding tissue.

[0032] It is another object of the invention to provide an implant thatis configured to have associated with it an angiogenic substance thatpromotes angiogenesis within tissue surrounding the implant.

[0033] It is another object of the invention to provide an implantconfigured to interact with blood present in the tissue into which theimplant is inserted.

[0034] It is another object of the invention to provide an implant thatdefines an interior into which blood can enter and thrombose.

[0035] It is another object of the invention to provide an implant towhich a thrombus of blood or an angiogenic substance can be insertedbefore or after the implant has been inserted into tissue.

BRIEF DESCRIPTION OF THE DRAWINGS

[0036] The foregoing and other objects and advantages of the inventionwill be appreciated more fully from the following further descriptionthereof, with reference to the accompanying diagrammatic drawingswherein:

[0037]FIG. 1A shows a side view of a spring implant embodiment in itssmall profile, first configuration;

[0038]FIG. 1B shows a side view of a spring implant embodiment in itslarge profile second configuration;

[0039]FIG. 1C shows an alternate spring implant embodiment in its smallprofile first configuration;

[0040]FIG. 1D shows an alternate spring implant embodiment in its largeprofile second configuration;

[0041]FIG. 2A is a side view of the spring implant embodiment in its lowprofile, first configuration being delivered to a tissue location;

[0042]FIG. 2B is a diagrammatical sectional illustration of the implantexpanded to its second configuration within a tissue location;

[0043]FIG. 2C shows a side view of the alternate spring embodimentmounted on a delivery device;

[0044]FIG. 3 shows a sectional illustration of the left ventricle of ahuman heart having several implants of the present invention;

[0045] FIGS. 4A-4D show a sectional illustration of the left ventricleof a human heart with a steerable delivery catheter positioned withinthe ventricle to deliver implants into the myocardium;

[0046]FIG. 5A shows a side view of a mesh tube implant in its lowprofile first configuration;

[0047]FIG. 5B shows a side view of a mesh tube implant in its largeprofile second configuration;

[0048]FIG. 5C shows a detailed view of the band of the mesh tubeembodiment;

[0049]FIG. 6A shows a side view of the mesh tube embodiment in its lowprofile first configuration being delivered into a tissue location;

[0050]FIG. 6B shows a sectional illustration of the mesh tube implantits large profile, second configuration residing within tissue;

[0051]FIG. 7A shows a perspective view of a rolled tube implant in itssmall profile first configuration;

[0052]FIG. 7B shows a perspective view of the rolled tube implant in itslarge profile second configuration;

[0053]FIG. 8A is a side view of a sheet of material used to form therolled tube implant;

[0054]FIG. 8B shows an end view of a sheet of material used to form therolled tube implant;

[0055]FIG. 9A is a side view and partial cut-away view of the rolledtube implant being delivered to a tissue location through a deliverydevice;

[0056]FIG. 9B is a cross-sectional view taken along the line 9A-9B ofFIG. 9A;

[0057]FIG. 9C is a side view illustration of the rolled tube implantplaced within tissue and expanded into its second configuration;

[0058]FIG. 9D is a cross-sectional view of the rolled tube implantviewed along the line 9D in FIG. 9C;

[0059]FIG. 10A is a perspective view of an implant comprising a spineand plurality of rings in its small profile first configuration;

[0060]FIG. 10B is a perspective view of the implant comprised of a spineand plurality of rings in its large profile second configuration;

[0061]FIG. 11A is a side view of the implant comprised of a spine andplurality of rings in its low profile, first configuration beingdelivered to a tissue location;

[0062]FIG. 11B is a cross-sectional view of the implant comprised of aspine and a plurality of rings viewed along the line 11B-11B in FIG.11A;

[0063]FIG. 11C is a section side view of the implant comprised of aspine and plurality of rings in its large profile, second configurationplaced within tissue;

[0064]FIG. 11D is a cross-sectional view of the implant comprised of aspine and a plurality of rings viewed along the line 11D-11D in FIG.11C;

[0065]FIG. 12A is a side view of a bifurcated implant in its low profilefirst configuration;

[0066]FIG. 12B is a front view of a bifurcated implant in its lowprofile first configuration;

[0067]FIG. 12C is a side view of a bifurcated implant in its largeprofile second configuration;

[0068]FIG. 12D is a front view of a bifurcated implant in its largeprofile second configuration;

[0069]FIG. 13 is a side view of an alternate bifurcated implant having aslanted piercing edge in its low profile first configuration;

[0070]FIG. 14A is a side view of a bifurcated implant in its lowprofile. first configuration being delivered to a tissue location;

[0071]FIG. 14B is a sectional side view of a bifurcated implant in itslarge profile, second configuration placed within tissue;

[0072]FIG. 15A is a top view of a bifurcated open spring implant in itslow profile first configuration;

[0073]FIG. 15B is a top view of a open spring bifurcated implant in itslarge profile second configuration;

[0074]FIG. 15C is a side view of an open spring bifurcated implant inits low profile first configuration;

[0075]FIG. 15D is a side view of an open spring bifurcated implant inits large profile second configuration;

[0076]FIG. 16A is a side view of an open spring bifurcated implant beingdelivered to a tissue location;

[0077]FIG. 16B is a sectional side view of an open spring bifurcatedimplant located within tissue and expanded to its large profile secondconfiguration;

[0078]FIG. 17A is a top view of a bifurcated spine and hoop implant inits low profile first configuration;

[0079]FIG. 17B is a top view of a bifurcated spine and hoop implant inits large profile second configuration;

[0080]FIG. 17C is a side view of a bifurcated spine and hoop implant inits low profile first configuration;

[0081]FIG. 17D is a side view of a bifurcated spine and hoop implant inits large profile second configuration;

[0082]FIG. 18A is a side view of a bifurcated spine and hoop implant inits low profile, first configuration being delivered to a tissuelocation;

[0083]FIG. 18B is a sectional side view of a bifurcated spine and hoopimplant placed within tissue and expanded to its large profile secondconfiguration;

[0084]FIG. 19A is a side view of a flexible brush implant.

[0085]FIG. 19B is an end view of the flexible brush implant.

[0086]FIG. 19C is a side view of the flexible brush implant at its postdelivery configuration.

[0087]FIG. 19D is a side view of a flexible brush implant having a coreformed of twisted wires;

[0088]FIG. 19E is a section view of the flexible brush implant show inFIG. 19D;

[0089]FIG. 19F is a partial cut-away view of the flexible brush implantand associated delivery system penetrating the intended tissue location;

[0090]FIG. 19G is a partial cut-away view of an implanted flexible brushimplant and its associated delivery system being withdrawn.

DESCRIPTION OF THE ILLUSTRATIVE EMBODIMENT

[0091]FIGS. 1A and 1B show a first embodiment of the implant comprisinga helical coil spring 10. The spring is formed from a filament 12 offlexible material such as stainless steel or other metal or high densitypolymer. The filament is helically wrapped to form several individualcoils 14 that comprise a spring having an interior 15. At each end 16 ofthe spring, the filament 12 terminates with a small tab 18 extending ina plane parallel to the axis of the implant. The tabs 18 are used formaintaining the implant upon the delivery device as will be described infurther detail below. FIGS. 1C and 1D show an alternative spring implantembodiment 26 comprised of two segments 27 that are wound in oppositedirections and joined together by a bridge 29. Each segment has a freeend 30 in which the filament 12 terminates in a bulbous tab 18.

[0092] The spring implant embodiments are easily arranged from a firstconfiguration to a second configuration, where the second configurationof the implant has a larger profile than that presented while in thefirst configuration. Profile may be defined as the maximum width, or inthe case of a coil, the diameter, of the device. FIGS. 1A and 1C showthe device in a small profile, first configuration that is suitable fordelivery of the device into the tissue. FIGS. 1B and 1C show the implantdevices in a larger profile, second configuration into which the implantis transformed after delivery to place surrounding tissue in stress.

[0093] In its first configuration, shown in FIGS. 1A and 1C, the springis wrapped more tightly, having a longer length L₁ and more coils 14 andthus a smaller diameter D₁ than in the second configuration shown inFIGS. 1B and 1D. In the second configuration, shown in FIGS. 1B and 1D,the diameter D₂ is greater than D₁ and L₂ is less than L₁ because thespring has expanded, becoming less tightly wound and having fewer coils14. The alternate, double spring embodiment resiliently expands from itsrestrained first configuration to its larger profile, secondconfiguration more gradually than does the single spring implant 10. Thecounter rotation of the oppositely wound spring segments 28 serves toslow the unwinding of the device, thereby providing control over themagnitude of injury experienced by the surrounding tissue.

[0094] The implant is more easily delivered into the intended tissuelocation while in the first configuration of FIGS. 1A and 1C. Thereduced profile presented by the spring in a smaller diameter D₁, on theorder of 1.0-1.5 mm, can more easily penetrate tissue. A channel neednot be preformed by removing tissue through coring or laser techniquesto place the implants. The implants are not intended to maintain apatent channel through the subject tissue through which blood can flow.The implants of the present invention induce angiogenesis by interactingwith the tissue and blood already in the area into which they areplaced. Once implanted in the tissue, the expansion of the implant toits larger profile, second configuration, on the order of 2.0-2.5 mm,serves not only to help anchor the implant within the tissue, but alsoserves to irritate and injure the surrounding tissue into which it isimplanted. Preferably, the spring embodiments are fabricated to have anunstressed configuration equivalent to the second configuration shown inFIGS. 1B and 1D as this will be the final implanted configuration of thedevice after release from its delivery device. The expanding implantsmay rupture and push aside tissue, which permits the inflow andcollection of blood from the surrounding area. However, maintaining apatent channel for blood flow through the implant is not necessary.

[0095] A more important aspect of the presence of the implants is thatinjury response exhibited by the surrounding ischemic tissue ismaximized and angiogenesis is initiated by the resulting thrombosis andfibrin growth as described above. The implants remain expanded againstthe surrounding tissue after implantation becoming clotted withthrombosis and fibrin growth throughout the implant structure. After thenew tissue has surrounded and ingrown the implant new vessel growth willemerge in the region to supply the new tissue. At this advanced stage ofinjury response and healing, the stress applied on surrounding tissue bythe expanded implant may be minimal or nonexistent because tissue hasgrown around and accommodated the implant.

[0096] Access to ischemic tissue sites within a patient to deliver theimplants of the present invention may be accomplished percutaneously,surgically by a cut-down method orthoracically. However, the lessinvasive and traumatic percutaneous approach of delivering the implantsis generally preferred. A percutaneous delivery device for deliveringthe implants to the myocardium of the heart is shown in FIGS. 2A-2C.FIG. 3 shows a diagrammatic sectional view of the left ventricle 2 of ahuman heart 1 into which the delivery device gains access. Each of theimplant embodiments described herein may be delivered percutaneouslythrough a delivery catheter 36, shown in FIGS. 4A-4D, as will bedescribed in detail below. It is noted that, throughout the descriptionof the implant embodiments and their associated delivery systems,“proximal” refers to the direction along the delivery pathway leadingexternal to the patient and “distal” refers to the direction along thedelivery pathway internal of the patient.

[0097] To reach the left ventricle of the heart percutaneously, a guidecatheter (not shown) is first navigated through the patient's vessels toreach the left ventricle 2 of the heart 1. A barb tipped guidewire 34may then be inserted through the guide catheter and into the ventriclewhere it pierces the myocardium 4 and becomes anchored within thetissue. After anchoring the guidewire, a steerable implant deliverycatheter 36 may be advanced over the guidewire to become positionedwithin the ventricle for delivery of the implants. To facilitatedelivery of multiple implants, the guidewire lumen of the deliverycatheter 36 may be eccentrically located on the catheter 36. Therefore,when the catheter is rotated about the guidewire, the center of thecatheter will rotate through a circular path as demonstrated in FIGS. 4Cand 4D, to encompass a broader delivery area with one guidewireplacement. The outside diameter of the delivery catheter is preferablyless than 0.100 inch. Additionally, the delivery catheter may beprovided with steering capability by means of a pull wire extending thelength of the catheter and attached at its distal end such that pullingon the wire from the proximal end causes the distal tip of the catheterto be deflected. Steering capability thus provides a broader range ofdelivery area with a single catheterization. A detailed description ofthe construction of the steerable delivery catheter 36 for reachingmultiple sites within the left ventricle is described in U.S. patentapplication Ser. No. 09/073,118 filed May 5, 1998, the entirety of whichis herein incorporated by reference.

[0098]FIGS. 2A and 2B show the delivery of the spring implant 10 intotissue. The implant may be carried to the delivery location over aflexible push tube 20 that is slidable through the steerable deliverycatheter 36. FIG. 2C shows the alternate embodiment of the springimplant 26 mounted on the push tube 20. The push tube over which thespring implants are carried may be an elongate flexible hypodermic tubeand be configured to have a sharp distal end 22 for piercing the surfaceof tissue into which the implant will be placed. Additionally, the pushtube slidably receives a release wire 21, which extends through threadloops 24 that pass through side holes 25 at the distal end of the pushtube 20 and wrap around tabs 18 of the spring. In the case of thealternate embodiment, a thread loop 24 extends from the release wire,through a side hole to capture the bridge 29 as well. By theinterlocking of the thread loops with the release wire within the pushtube, the ends 16 of the spring are held close to the push tube 20 tomaintain a tightly wrapped diameter, extended length, firstconfiguration during delivery of the device into the tissue. The tabs 18preferably have a bulbous configuration of greater diameter than thefilament 12 to prevent the tabs from slipping through the thread loop.

[0099] After being advanced through the delivery catheter 36 which hasbeen placed adjacent tissue to be treated, the push wire 20 is advanceddistally, independently of the delivery catheter 36, so that the sharpdistal tip 22 pierces the tissue, as shown in FIG. 2A. Continued furtherdistal movement of the push wire 20 advances the implant into the tissuewhere it can be released to assume its second configuration having agreater profile than the first configuration. The depth to which theimplant is placed within the tissue is not believed to be a significantfactor in the ultimate success of the device, however, placement withinthe tissue within an area believed to have the most significant amountof vascular activity is desirable. For example in the case of myocardialtissue, it has been observed that areas closer to the endocardialsurface are generally more active to create pumping action in themyocardium than are areas closer to the epicardial surface. Therefore,when placing implants in myocardial tissue, placement near theendocardial surface is preferred, though it is not necessary to placethe implant flush with the surface. It is understood that an area ofactive, moving muscle tissue will cause the implants of the presentinvention to flex, at least slightly with the surrounding tissue duringthe cardiac cycle.

[0100] Once the implant is located within the tissue, release wire 21 iswithdrawn proximally relative to the push tube 20. Thread loops becomereleased from the wire 21 and are free to pass through side holes 25 asthe spring resiliently expands to its second, large profileconfiguration, within the tissue. The greater profile and increaseddiameter of the implant in the second configuration puts an immediatestress on the surrounding tissue causing some tearing . After expansionto the second configuration, the surrounding tissue 4 may tend toherniate into the implant device at herniation points 28 located betweenthe coils 14 of the implant. After implantation, the push tube 20 iswithdrawn proximally through the interior 15 of the implant and backinto the delivery catheter 36 together with the release wire, and theassembly withdrawn from the patient. The thread loops 24, preferablyabsorbable suture material, may be left behind, attached to the implant.

[0101] In the case of implants placed within myocardial tissue 4 of theheart 1, several implants 8 may be placed within a region of ischemictissue as shown in FIG. 3. The implants 8 generally expand to a diameterof approximately 2 mm and are preferably spaced so that each implantserves an area of one square centimeter. Though any number of implantsmay be placed, the density of approximately one per square centimeter ispreferred so as not to interfere with the muscular function of thetissue to which they are implanted. In other words, many implants withina certain area could potentially interfere with the motion of the muscletissue to the detriment of other necessary functions of that tissue.Multiple implants are delivered to a given tissue location by repeatingthe steps recited for delivering a single implant.

[0102] In addition to inducing an injury response by expanding withinthe tissue, the implants induce angiogenesis within the surroundingtissue 4 by other mechanisms. One such mechanism is a process ofthrombosis of the blood surrounding an implanted device 10 and beingpermitted to pool within the interior 15 of the device. Blood that poolsaround the implant or in the implant thrombosis which leads to fibringrowth and nucleation of arterioles that become vessels to supply bloodto the healed region. This process may be further enhanced byapplication of an angiogenic substance to the implant device. Thesubstance may be a solid or fluid placed within the interior 15 of thedevice before or after delivery of the implant so that it comes intocontact with and is distributed by blood entering and surrounding theimplant. To deliver the angiogenic substance to the implant after it hasbeen delivered into tissue, the delivery device may be configured as aconduit through which the substance can be transmitted and released intothe implant while the delivery device and implant are still associated.In the case of the tubes and catheters discussed above in connectionwith a percutaneous delivery technique, the angiogenic substance may beadvanced from the proximal end of the tube, outside the patient, throughthe lumen of the tube and expelled from a port at the distal end of thetube and into or around the implanted device. Alternatively, theangiogenic substance may be coated onto the device or the device may bemade from such a substance.

[0103] Another embodiment of the vascular inducing implants is shown inFIG. 5A. A mesh tube implant 40 is shown in its low profile firstconfiguration, suitable for delivery into tissue. The mesh tube iscomprised of a mesh pattern of wire like elements 42 that are formedfrom a material that is flexible yet sufficiently rigid to maintain anexpanded, second configuration having a larger profile than its firstconfiguration. The mesh tube embodiment may be fabricated from a thinmetal sheet etched out a pattern of spaces or openings and then rolledand the ends joined to form a tube. Alternatively, the implant may beformed from a fabric such as dacron rolled into a tubular shape. In apreferred embodiment, the braided tube is formed from wire elements 42woven together to form a tube with the elements slidable relative toeach other. The mesh may be resiliently expandable, remaining expandedby the inherent resilience of the material selected, such as highlyelastic or high tensile strength material. Alternatively the mesh tubemay be plastically deformed to its second configuration, if the elementsare formed from a malleable alloy.

[0104] In the wire mesh tube embodiment, the wire ends 46 are joined torings 44. As shown in FIG. 5C the ends 46 of the wire elements 42 may bejoined to the end ring 44 at connections 48. The rings 44 may be polymertubes heat shrunk to the element ends to form the connections.Alternatively, the rings may be stainless steel, connected to theelements by solder joints. The elements may be fabricated to be movablerelative to the ring 44. Although not shown, the ends 46 of the elementsmay be formed to have eyelets that are threaded around a narrow end ring44. Thus, the elements would be free to adjust their position along thering during expansion from the first to the second configuration.Additionally, as shown in FIG. 5C, the ring 44 may be non-continuous,having a split 50 across its surface to promote expandability. In thisconfiguration, the ring 44 may provide the supporting force to keep theimplant in its expanded second configuration. The split 50 in the ring44 permits the ring to be coiled into a small configuration fordelivery, yet expand and uncoil into a larger configuration.

[0105] The ring 44 may be resiliently expandable, whereby its naturaltendency is to have an uncoiled configuration and maximum diameter. Inthis embodiment, the ring is confined in a coiled smaller diameterduring delivery to the intended tissue location and is released touncoil and resiliently expand to its larger configuration once placed inthe tissue. The elements 42 join to the rings 44 at both ends of themesh tube embodiment thus slide into the second, larger profileconfiguration under the force of the resilient rings 44. Alternatively,the rings 44 may be plastically deformable so that they expand alongwith the movement of the elements 42 of the mesh tube 40 as the lengthof the tube is compressed to cause radial expansion.

[0106] The mesh tube implant may be delivered over a delivery systemcomprising a relatively stiff small diameter tube 52, such as a hypotubehaving slidable within its central lumen a piercing release wire 54 asshown in FIGS. 6A and 6B. In FIG. 6A the mesh tube 40 is supported fromlongitudinal movement at its proximal end 56 by a stop 60 mounted on theexterior of the hypotube 52. The distal end 58 of the mesh tube issupported from longitudinal movement by a small catch member 62 mountedon the exterior of the release wire 54. Both the catch 62 and the stop60 engage the rings 44 at the proximal and distal ends of the mesh tube40. The hypotube 52 and release wire 54 carrying the mesh tube 40 aredelivered to the intended tissue location through a previously placedsteerable catheter 36 as was described in connection with FIGS. 2A and2B. The steerable delivery catheter 36 is not shown in FIGS. 6A and 6Bbut is understood to be part of the delivery system. While tension isapplied on the mesh tube by placing slight pressure on the release wire54 in the distal direction and maintaining pressure on the hypotube 52in the proximal direction, the mesh tube is maintained in its lowprofile extended length first configuration. The combination is togethermoved distally toward the intended tissue location.

[0107] In the case of implantation in the myocardium, the sharp piercingdistal tip 64 of the release wire 54 penetrates the endocardial surface6 to provide access to the myocardium 4. After placement of the meshtube within the myocardium 4, it is expanded to its second configurationby moving the hypotube, which engages the proximal end 56 of the tube,in a proximal direction while moving the catch 62 on the release wire 54in a proximal direction. Thus the ends 58 and 56 of the mesh tube aremoved closer, thereby shortening the length of the tube and causing itto expand radially, placing stress on the surrounding myocardial tissue4. After expansion of the mesh tube, the release wire 54 may bewithdrawn proximally so that its piercing distal tip 64 is within thehypotube 52. The combination can then be withdrawn from the patientwithout risk of injury to vessels from the sharp tip during withdrawal.

[0108]FIGS. 7A and 7B show yet another embodiment of the vascularinducing implant comprising a resiliently expandable rolled tube 70. Therolled tube may be fabricated from a flat sheet 72, as shown in FIG. 8Aand 8B. The material is preferably flexible, but will maintain aresilient energy after being bent into a tubular shape tending tomaintain the tube in a relatively expanded, large diameterconfiguration. A metal such as stainless steel or a high density polymeris a preferred material. The tube material may be a solid or may beporous such as a mesh screen. The flat sheet is preferably configured tohave formed along one longitudinal edge 76 a tubular ridge 78 that willserve as a lock for holding the sheet in a tubular configuration whilebeing delivered to the tissue location, as will be described in furtherdetail below. The tubular ridge 78 may be a separate tubular segmentthat is attached to the flat sheet 72 by bonding such as adhesive,soldering or welding. Alternatively the tubular ridge may be formed bycurving over a longitudinal edge 72 of the sheet to define a tube alongthat edge.

[0109] Placing the flat sheet into the low profile first configurationrequires rolling the flat sheet 72 into a tightly wound roll to definethe cylindrical structure of the tubular implant 70. In this firstconfiguration, the rolled tube may be coiled upon itself several timesto form a small outer diameter D, as shown in FIG. 7A. Force is requiredto maintain the rolled tube implant in the first configuration becausethe elastically deformed sheet material 72 naturally tends to the largerdiameter D₂ of the second configuration shown in FIG. 7B. The rolledtube is implanted in the tissue in the first configuration shown in FIG.7A and permitted to expand to its equilibrium configuration representedin FIG. 7B having a larger profile (diameter) than the firstconfiguration.

[0110] As with the other embodiments, the expansion of the rolled tubewithin the subject tissue creates slight injury to the tissuesurrounding the implant as well as provides a device for interactingwith blood from the surrounding tissue to initiate the process ofangiogenesis as was described above. In the case of a rolled-tube formedfrom a porous or mesh material, further injury to the tissue whichsurrounds the implant is expected due to the rough surface of theimplant material and constant dynamic contact with the tissue.Additionally, the porous or mesh material may enhance fibrin growththrough the device to further enhance angiogenesis.

[0111] Delivery of the rolled tube embodiment 70 is shown in FIGS. 9Aand 9B. As with the other implant embodiments of the present invention,the rolled tube embodiment may be delivered to the subject tissuepercutaneously, thoracically or surgically by a cut-down method. Indelivering the implant to myocardial tissue of the heart, percutaneousdelivery is preferred because it is least invasive and traumatic to thepatient. FIGS. 9A-9D depict delivery of the rolled tube implantpercutaneously to the myocardial tissue 4 of the heart. After the leftventricle 2 has been accessed by a steerable delivery catheter 36 asdescribed above, the delivery catheter is anchored in position adjacentthe intended tissue location by a barbed tip guidewire 34 that extendsthrough an eccentric guidewire lumen 32 of the delivery catheter. Thebarbed tip guidewire is anchored in the myocardial tissue 4. The rolledtube 70 is carried through the central lumen 38 of the delivery catheter36 over a coaxial arrangement of a push tube 80 and piercing wire 82having a piercing distal tip 84. The piercing wire 82 is longitudinallyslidable with respect to the push tube 80 so that it may be extendedrelative to the push tube to release the rolled tube as will bedescribed below.

[0112] The push wire has formed along its length a backstop 86configured as a disk radially extending from the push tube to providesurface against which the proximal end 88 of the rolled tube can abutduring delivery. To restrain the rolled tube in its first configurationduring delivery, the backstop may additionally have two longitudinallyand distally extending protrusions 90 and 92. The inner protrusion 90extending within the interior of the tubular ridge 78, which is arrangedto be at the edge of the outermost coil 93 of the rolled tube duringdelivery. The outer protrusion 92 holds the outermost coil 93 from itsouter surface, working in conjunction with the inner protrusion tomaintain the tube in its small diameter first configuration against theresilient expansive force inherent in the rolled tube. The distal end 94of the rolled tube is supported in its compact first configuration by aproximally and longitudinally extending protrusion 96 which resides inthe interior 79 of the tubular ridge 78 at the distal end 94 of therolled tube. The protrusion 96 extends proximally from the sharpeneddistal end 84 of the piercing wire 82.

[0113] With the rolled tube located between the protrusions 90, 92 atthe proximal end 88 and piercing wire 82 extending through its interior74. With the sharpened distal end 84 protruding from the distal end 94of the rolled tube to pierce the tissue into which it is to bedelivered. The protrusion 96 extends proximally, back into the interior74 of the tube. In this configuration, the push tube, piercing wire androlled tube combination is advanced, together, distally out of thedistal end of the delivery catheter 36 as shown in FIG. 9B so that thepiercing distal tip 84 of the piercing wire penetrates the surface ofthe tissue 6. The assembly is advanced distally into the tissue 4 to adepth that receives the entire implant as shown in FIG. 9D. The proximalend 88 of the implant may, but need not be flush with the surface 6 ofthe tissue 4.

[0114] After the tube is delivered into the tissue, the piercing wire 82is moved distally and the push tube 80 is moved proximally, in oppositedirections relative to each other, so that the backstop 86 andprotrusions 90, 92 and 96 move away from the ends of the tube, releasingit from the confined, first configuration so that it expands to itssecond, larger profile configuration shown in FIGS. 9C and 9D. After thetube is released from the push tube and piercing wire, the piercing wireis withdrawn proximally through the interior 74 of the now expandedrolled tube 70 into the push tube 80, which is then withdrawn into thedelivery catheter 36. The barbed tip guidewire 34 is then pulled fromits anchored location within the tissue 4 and the entire deliverycatheter 36 is withdrawn from the patient.

[0115]FIG. 10A shows another embodiment of the vascular inducingimplants. A spine implant 100 is comprised of a plurality of expandablec-shaped rings 102 concentrically arranged along an axial support orspine 104. Each ring is joined to the spine at a point along theircircumference. The spine is tangent to each ring 102, with each ringlying in a plane that is normal to the axis of the spine. Adiscontinuity 106 at the top of each ring permits the rings to expandbetween two configurations: a first, low profile configuration in whichthe ends 108 of the ring overlap to define a ring of relatively smalldiameter and a second configuration that presents a larger profile, inwhich the leaves of the ring are open and do not overlap defining alarger diameter and profile.

[0116] The spine implant embodiment may be a unitary structure formedfrom an elastically deformable material such as a plastic or stainlesssteel. Alternatively, the rings 102 may be separate components that areadjoined to the spine by welding, soldering or bonding. The ends of eachring are preferably formed to have eyelets 110. By locking the eyelets110 together, the resiliently expandable rings 102 may be maintained ina reduced profile, closed configuration, against the inherent expansiveforce. An elongate release pin 112, shown in phantom in FIG. 10A, may beinserted through the aligned eyelet pairs of all the closed rings on thespine. The pull pin 112 may be inserted through the eyelets to maintainthe rings 102 in a closed configuration by maintaining each ring 102 ina closed configuration, with the eyelets 110 aligned concentrically. Therings 102 may be expanded after implantation within the tissue bypulling the pin from the eyelets to release the rings and permitresilient expansion as will be described in further detail below.

[0117] FIGS. 11A-11D illustrate the delivery of the spine implant 100.FIGS. 11A and 11B show the implant in its first, low profileconfiguration, which is maintained during deliver and insertion into theintended tissue location. As with the other embodiments described above,the implantation of the device will be described as it is implanted intomyocardial tissue of the heart. Although the device may be delivered bya variety of methods including surgically or thoracically, the preferredmethod of delivery is percutaneous, accessing the myocardium 4 throughthe left ventricle of the heart as is shown in FIGS. 4A-4D.

[0118] The spine implant 100 is delivered over a push wire 114 that isslidable through the delivery catheter 36. The push wire extends throughthe center of the rings during delivery while they are in their closed,small profile configuration. The push wire 114 may be of a diameterwhich is approximately the same size as the inside diameter of the ringsin their closed, small profile configuration to remove any slack betweenthe implant and the push wire during delivery. The pull pin 112 extendsthrough the eyelets 110 and is parallel with the push wire 114 throughthe delivery catheter 36 where it can be manipulated independently ofthe push wire at its proximal end extending outside the patient.

[0119] The push wire 114 has a sharpened distal end 118 that is capableof piercing the tissue surface 6 to provide an entry site into which theimplant may be inserted into the tissue 4. To prevent proximal movementof the implant on the push wire during delivery into the tissue 4,either the pull pin 112 or the push wire 114 may have formed on itssurface a backstop against which the most proximal ring 102 can abut toresist distal movement. After insertion of the implant into the tissue,the pull pin 112 may be pulled proximally to be removed from the eyeletsof the rings 110 permitting them to resiliently expand to the openconfiguration as shown in FIGS. 11C and 11D. After the pull pin has beenwithdrawn to expand the implant to its second, larger profileconfiguration, the push wire 114 may be withdrawn proximally through thecenter of the rings and out of the tissue and the delivery devicewithdrawn from the patient.

[0120] FIGS. 12A-12D show another embodiment of the implant devicehaving a first configuration that is uniaxial and a second configurationin which a portion of the device becomes biaxial or bifurcated. Thebifurcated implant 120 is preferably a hollow unitary structureessentially comprised of three tubular sections arranged similar to apair of pants. Specifically, the implant has a trunk portion 122 havinga generally tubular configuration which splits into a first leg 124 anda second leg 126, each about one-half the diameter of the trunk portionand having a length that is approximately one-half the length of theentire implant. As shown in FIGS. 12A and 12B, the legs 124 and 126 areclosed, their longitudinal axes lying parallel to the central axis ofthe trunk portion 122. In this first configuration, the implant 120presents a low profile suitable for penetration and delivery intotissue.

[0121]FIGS. 12C and 12D show the implant in its second, large profileconfiguration wherein the legs 124 and 126 are split apart; curved awayfrom each other such that their axes approach an angle of 90° relativeto the central axis of the trunk portion 122. When moved to the secondconfiguration, the split legs of the implant serve to stress and injuresurrounding tissue into which the implant has been inserted. The tearingand abrasion of the tissue surrounding the now expanded legs 124 and 126respond to the injury through a healing process that leads toangiogenesis as described above. Additionally, because the legs stay intheir expanded configuration, the tissue continues to be irritated bythe presence of the implant, thereby continuing the injury response andinitiation of angiogenesis.

[0122]FIG. 13 shows a variation of the biaxial implant 120 having aslanted profile edge 130 formed along the ends of the legs 124 and 126to help to facilitate penetration through the tissue. Although the bluntedge tubular ends of the legs 124 and 126 as shown in FIGS. 12A-12D maybe suitable for penetrating soft tissue, the angled edge 130 shown inFIG. 13 provides a sharper profile to pierce tough layers of tissue. Theangled edge may be configured in many ways other than the sloping edgeshown in FIG. 13. For example, the second leg 126 may have an edge thatis angled in the reverse direction from the edge of leg 124 to form anarrowhead profile (not shown).

[0123] The biaxial implant may move from its first, compact profileconfiguration to its second, expanded profile configuration either byinherent resiliency of the implant material, or by a plasticdeformation. To expand the plastically deformable embodiment, asplitting force may be applied between the legs of the implant once ithas been inserted into tissue. The splitting force may be applied by apull wire extending through the interior of the implant, having a largeprofile distal tip that runs between the adjoining legs as the pull wireis moved in a proximal direction and removed from the center of theimplant through the trunk portion. Alternatively, and in a preferredmethod, the implant is resiliently expandable and may be delivered andexpanded to the extended tissue location over two guidewires as isdescribed in detail below.

[0124]FIGS. 14A and 14B illustrate the delivery of the bifurcatedimplant embodiment into tissue such as myocardial tissue 4 of themyocardium. As was described with relation to the other embodiments, thebifurcated embodiment is preferably delivered percutaneously to themyocardium through a steerable delivery catheter 36 that has beeninserted into the left ventricle of the heart adjacent the myocardialtissue to receive the implant. The bifurcated implant 120 is carriedthrough the delivery catheter 36 over a guide tube 132 sized to fitclosely the inside diameter of the trunk portion 122 of the implant.Through the guide tube 132 extends two support wires 134 and 136 thatextend through the trunk portion of the implant and into the legs 124and 126 during delivery. The support wires 134, 136 are relatively stiffto maintain the legs 124, 126 in their joined, low profile firstconfiguration as shown in FIG. 14A. The wires and guide tube areslidable relative to each other and through the delivery catheter 36.During delivery, the guide tube extends into the interior of the implantonly through the trunk portion 122. The support wires 134, 136 extenddistally beyond the trunk portion and into each leg to act as stiffeningmembers, providing axial support from the inside diameter of each leg toresist the resilient force of the legs to bend apart from each other.

[0125] During delivery, the entire assembly is moved distally, with theguide tube 132 and wires 134, 136 being pushed distally to expose theimplant from the distal end of the delivery catheter 36 so that it maypenetrate the endocardial surface 6 and enter the myocardium 4 as shownin FIG. 14B. The delivery force pushing the implant in the distaldirection is applied by the distal end of the guide tube 132 engagingthe junction of the legs 138. After the implant has been inserted intothe tissue 4, the support wires 134 and 136 are withdrawn proximallyfrom the legs 124, 126 of the implant permitting them to expand apartfrom each other to injure the surrounding tissue and place it in astressed condition that will be maintained by the implant in its secondconfiguration. In addition to providing a constant source of irritationand injury to the tissue, the expanded implant serves to resistmigration out of the tissue despite tissue movement because the implanthas clawed into the tissue during expansion. After deployment of theimplant the guide tube 132 and support wires 134, 136 are withdrawnfurther proximally, into the delivery catheter 36, which then may bewithdrawn from the patient.

[0126] Another embodiment of a bifurcated implant is shown in FIGS.15A-15D. The open spring bifurcated implant 140 is intended to have atrunk portion 142 and two leg portions 144 and 146 similar to thebifurcated embodiment discussed above. The open spring bifurcatedembodiment may comprise two helically wrapped coil springs 148, 150joined together only at the proximal end 152 of the trunk portion.Alternatively, the bifurcated spring embodiment may comprise a singlespring that is wound to double back upon itself at the proximal trunkcoil 152 and defining two legs 144 and 146 extending therefrom that aredefined by each end of a single spring. The coil spring should beflexible and capable of maintaining substantially its expandedbifurcated and larger profile configuration under the collapsing forceof the stressed tissue in which it is implanted.

[0127] The first, low profile configuration of the implant is shown inFIGS. 15A and 15C. The coils 152 of each of the legs 144 and 146interleave so that they substantially lie along the same longitudinalaxis as the trunk portion 142. In this configuration, the overallprofile of the implant 140 is minimized, facilitating delivery of theimplant into tissue. FIGS. 15B and 15D show the implant in its largerprofile second configuration. The free ends of each of the legs 144 and146 spring open, naturally inclined to the Y-shape bifurcatedconfiguration, because they are plastically deformed to have that shapeduring their formation. The profile of the implant is increased by themovement of the leg portions away from the axis of the trunk portion142. When permitted to expand within the subject ischemic tissue, theexpanding leg portions are expected to cause some minimal injury andpossible tearing of the tissue into which it is implanted. The injury,which will be continually irritated by the presence of the implant inits second configuration, is expected to instigate a healing response bythe tissue that will initiate angiogenesis by the mechanisms describedabove.

[0128]FIGS. 16A and 16D illustrate the steps of delivering thebifurcated open spring implant into ischemic tissue 4. In FIG. 16A, theimplant is maintained in its uniaxial, low profile first configurationby a relatively stiff piercing wire 158 having a sharpened distal tip160 for piercing the surface of the tissue 6. The piercing wire 158extends through the interior 162 of the spring embodiment, retaining thecoils 154 of the legs 144 and 146 along the central axis by contactingtheir inside surfaces. The legs are held against movement by thepresence of the wire 158. The sharpened tip 160 of the piercing wireprotrudes from the distal end of the implant so that it will be first tocontact the tissue during distal movement to the implant site.

[0129] Push tube 156 is slidable over the push wire and has a largerdiameter than the push wire, sized to engage the circumference of themost proximal coil 152 of the implant. The push tube delivers a pushingforce against the implant during insertion into the tissue, when boththe piercing wire 158 and push tube 156 are moved distally in unison tomaintain the piercing wire through the implant which is maintained inits first configuration. Also the push tube 156 can move independentlyof the piercing wire 158, so that once the implant has been delivered toa proper depth within the tissue 4, the piercing wire 158 may beretracted into the push tube as shown in FIG. 16B, to release the coils154 to their expanded second configuration. After delivery and releaseof the implant into the ischemic tissue, the push tube 156 and piercingwire 158 may be retracted proximally into the steerable deliverycatheter 36 and the entire assembly withdrawn from the patient.

[0130] FIGS. 17A-17D show a variation of the open spring bifurcatedimplant embodiment. The bifurcated loop implant 170 is comprised offirst and second spines 172, 174 each having a plurality of circularloops 176. The loops 176 are joined to the respective spines at a pointaround their circumference such that they are arranged substantiallyconcentrically. The spines 174, 172 share several common loops 176 in atrunk portion 178 of the implant. The free ends of the spines 172, 174form leg portions 180, 182 of the implant, respectively. The implant isshown in its first low profile configuration in FIGS. 17A and 17C.

[0131] In the first configuration, the loops 176 of both spines and thetrunk portion are interleaved and lie substantially along the samelongitudinal axis. In the expanded second configuration, the legportions 180 and 182 spring apart under the resilient force of thespines 172 and 174 which are preformed to have a curved configuration,yielding the large profile configuration shown in FIGS. 17B and 17D. Theimplant is delivered into the subject ischemic tissue 4 by the stepsdiscussed above in connection with the open spring bifurcated embodimentand which are illustrated in FIGS. 18A and 18B. The piercing wire andpush tube 158, 156, respectively, may be used to deliver the loopbifurcated implant 170 in the same manner as the open spring embodimentdescribed above.

[0132] Another implant embodiment is shown in FIGS. 19A-19D. A brushimplant 240 is comprised of a central core member 242 having a pluralityof resilient bristles 244 extending radially therefrom to irritatesurrounding tissue. The bristles 244 of the brush 240 collapse againstthe core 242 during distal movement into the tissue during delivery todefine a low profile fist configuration. After delivery into the tissuethe bristles resiliently expand in a radially outward direction, withrespect to the core, to define a larger profile second configurationthat irritates and places stress on surrounding tissue.

[0133] The central core member 242 is preferably somewhat rigid tofacilitate insertion into the tissue 4. The core may be solid or ahollow tube to define a central lumen 246 over which the implant can bedelivered into the intended tissue location. Additionally, the centrallumen 246 may contain an angiogenic substance to be delivered to theintended tissue location along with the implant. Alternatively, the core242 of the brush implant may be comprised of several wires helicallywrapped around each other along a single axis as shown in FIGS. 19D and19E. The brush implant shown in FIG. 19D is comprised of three helicallywrapped wires 248, 250 and 252 defining the core 242. Wedged in betweenthe wrapped wires are bristles 244 which extend radially from the core242. As shown in FIG. 19E, the three helically wrapped wires define acentral opening 254 through the center of the core. The central openingmay be useful for holding an angiogenic substance or thrombus of bloodwithin the implant that will later interact with blood flow afterimplantation. Additionally, the central opening 254 may receive aguidewire so that the implant may be delivered to its intended locationby tracking over the guidewire that has been inserted into a patient.Alternatively, the core 242 may be formed from only two separate wiresthat are helically wrapped about each other; however, a central opening254 may not be substantially defined by only two wires.

[0134] The bristles 244 attached to the core 242 serve injure andirritate surrounding tissue into which it is implanted to cause aninjury response that leads to angiogenesis. The bristles resilientlyextend from the core in a radially outward direction to place stress onsurrounding tissue and cause irritation. The bristles provide aplurality of contact points with the surrounding tissue where irritationoccurs, providing a plurality of nucleation sites where angiogenesis canbe initiated.

[0135] Tubes may be used in place of the wires that form the core 242and also the bristles 244. Tubular bristles and core wires providelumens that can retain a quantity of an angiogenic substance or thrombiof blood intended to interact with the surrounding tissue into which thedevice is implanted. The core wires may have an outside diameter of0.008 inch and the bristles may have an outside diameter on the order of0.006 inch to 0.010 inch. The bristles may be made from stainless steelor plastic.

[0136] As with the embodiments described above, the brush implant may bedelivered percutaneously, thoracically or surgically via a cut-downmethod to the intended tissue location. By way of example, FIG. 19Frepresents the brush implant being delivered percutaneously into themyocardium 4. A suitable delivery system for the brush type implant mayinclude a steerable outer catheter 36 within which a slidable smallerdiameter brush carrier catheter 260 having a central lumen 262. Thedistal end 264 of the brush carrier catheter is sharpened to be capableof piercing the endocardial surface of the myocardium 8.

[0137] A brush implant 240 is pushed through the central lumen 262 ofthe catheter 260 in a distal direction by a push wire 266 that is alsosized to fit within a central lumen of the catheter. Therefore, todeliver a brush implant into tissue, the distal end of the steerablecatheter 36 is brought in proximity to the intended tissue location asshown in FIGS. 19F and 19G. The brush carrier catheter carrying a brushimplant 240 and push wire 266 within its central lumen 262 is navigateddistally through the steerable catheter and out its distal end so thatthe sharpened distal end 264 of the catheter will pierce the surface ofthe tissue to permit delivery of the implant. After the distal end ofthe catheter has been advanced slightly into the tissue 4, the push wire266 is moved distally to push the brush implant 240 out of the distalopening 268 of the catheter 260.

[0138] Alternatively, the distal end of the brush carrier catheter 264need not be sharpened to pierce the tissue implant location. Rather, thebrush implant itself may have a sharpened distal tip 270 formed by thewrapped wires or hypotube of the core 242 that is capable of penetratingthe tissue 4 with pushing force provided from the push wire 266. Afterimplantation, the push wire 266 and brush carrier catheter 266 may bewithdrawn proximally back into the steerable catheter 36 and the implantsystem 258 withdrawn from the patient. The distal movement through thetissue that occurs during implantation causes the bristles 244 tomaintain an acute angle with a longitudinal axis of the brush implant,pointing in the proximal direction. After the brush is implanted, thebristles tend to resiliently return to a radially outward extendingposition that places stress on the surrounding tissue and causesirritation. Additionally, the bristles act as barbs to prevent proximalmigration of the implant.

[0139] From the foregoing it will be appreciated that the inventionprovides an implant and delivery system for promoting angiogenesiswithin ischemic, viable tissue. The invention is particularlyadvantageous in promoting angiogenesis with an ischemic myocardialtissue of the heart. The implants are simple and readily insertable intothe intended tissue location with a minimum of steps. The deliverysystems are simple to operate to implant the devices quickly and safely.

[0140] It should be understood, however, that the foregoing descriptionof the invention is intended to be illustrative thereof and that othermodifications, embodiments and equivalents may be apparent to thoseskilled in the art without departing from its spirit.

Having thus described the invention what we desire to claim and secureby Letters Patent is:
 1. An implant device for implantation intoischemic tissue comprising: an implant having a first configuration witha first profile and a second configuration having a second profile thatis greater than the first profile whereby surrounding tissue into whichthe implant is placed in stress and is irritated sufficiently to causean injury response including thrombosis formation that initiatesangiogenesis.
 2. An implant as defined in claim 1 further comprising aspring that is resiliently expandable from the first configuration tothe second configuration.
 3. An implant device as defined in claim 1wherein the implant defines a hollow interior.
 4. An implant device asdefined in claim 1 wherein the implant is flexible after assuming thesecond configuration.
 5. An implant device as defined in claim 1 furthercomprising an angiogenic substance for promoting angiogenesis isassociated with the implant.
 6. An implant device as defined in claim 5wherein the angiogenic substance is joined to the device by a coating.7. A device as defined in claim 5 wherein the angiogenic substancebecomes associated with the device after the device is delivered intothe tissue.
 8. An implant device as defined in claim 7 wherein the bodyof the device defines a hollow interior and the angiogenic substance isinserted into the hollow interior after the device is implanted.
 9. Animplant device as defined in claim 3 further comprising an angiogenicsubstance loaded into the hollow interior prior to implantation of thedevice.
 10. An implant device as defined in claim 9 further comprisingat least one opening in the body of a size to permit the angiogenicsubstance to transfer from the interior to the outside of the device.11. An implant device as defined in claim 5 wherein the angiogenicsubstance becomes associated with the implant after it is implanted. 12.An implant device as defined in claim 2 wherein the implant is acylinder.
 13. An implant device as defined in claim 2 wherein theimplant is bifurcated.
 14. An implant device as defined in claim 2wherein a first portion of the body remains static during and afterdelivery and a second portion of the body moves to a different positionrelative to the first portion after implantation to comprise a secondconfiguration of the device.
 15. An implant device as defined in claim14 wherein the implant comprises an elastic material and themotivational energy to cause the implant to move from the first to thesecond configuration is the inherent resiliency of the material.
 16. Animplant device as defined in claim 15 wherein the first portion is acylinder and the second portion is defined by at least one cylinder,smaller than the cylinder of the first portion, extending from andattached to the first portion at one end, and a second end being free.17. An implant device as defined in claim 16 wherein the free end of thesecond portion is configured to pierce the tissue.
 18. An implant deviceas defined on claim 15 wherein the first portion of the body is definedby an axial member and the second portion being defined by a pluralityof C-shaped rings joined to the axial member and lying within a planethat is substantially perpendicular to the axial member.
 19. An implantdevice as defined in claim 2 wherein the body is comprised of a tuberolled from a flat sheet.
 20. A method of promoting angiogenesis inischemic tissue comprising the steps of: accessing the ischemic tissue,inserting an implant into the tissue, orienting the implant in thetissue to place the tissue in stress.
 21. A method of promotingangiogenesis in ischemic tissue as defined in claim 20 wherein: the stepof orienting the implant to place the tissue in stress further comprisesexpanding the implant from a low profile first configuration to a largeprofile second configuration.
 22. A method of promoting angiogenesis asdefined in claim 22 comprising the further step of associating aangiogenic substance with the device after it is implanted.
 24. A methodof promoting angiogenesis as defined in claim 22 wherein the implantcomprises a body having an interior containing an angiogenic substanceto promote angiogenesis.
 25. A method of promoting angiogenesis inischemic tissue comprising: irritating the tissue sufficiently to causean injury response in the tissue that includes thrombosis and initiatesangiogenesis.
 26. A method of promoting angiogenesis as defined in claim25 wherein the tissue irritation is caused by the presence of a implantin the tissue.
 27. A method as defined in claim 26 wherein the implantsare implanted entirely and only within the myocardium.
 28. A method ofpromoting angiogenesis as defined in claim 26 wherein the implant isexpanded from a first configuration to a second configuration ofincreased profile to cause tissue injury.
 29. A method of promotingangiogenesis as defined in claim 26 wherein the tissue is myocardialtissue.
 30. A delivery device for placing an implant in the myocardiumof a patient comprising: a steerable delivery catheter having at leastone lumen and a defined length; an elongate shaft slidable through thelumen the delivery catheter having a proximal end, a sharpened distalend capable of piercing tissue and a length greater than the length ofthe delivery catheter; means at the distal end of the shaft forreleasably retaining the implant in a low profile first configurationand configured to release the implant to a large profile secondconfiguration.
 31. A method of percutaneously delivering an implant tomyocardial tissue comprising: providing an implant having a low profilefirst configuration and a large profile second configuration; providinga delivery catheter having proximal and distal ends and at least onelumen defined between the ends; providing an elongate shaft slidablethrough the lumen of the delivery catheter, having a sharp distal endand means for releasably retaining the implant in its firstconfiguration at the distal end of the shaft; inserting the deliverycatheter in the patient and navigating it through the patient's vesselsto the left ventricle and positioning the distal end adjacent myocardialtissue; advancing the shaft, with the implant retained on the distalend, through the lumen of the delivery catheter so that so that thesharp distal end of the shaft and implant protrude from the distal endof the catheter and penetrate the myocardium; positioning the implant tothe desired depth in the myocardium; releasing the implant from thedistal end of the shaft so that it expands to its second configurationin the myocardium; withdrawing the shaft and delivery catheter from thepatient.
 32. An implant as defined in claim 1 wherein the implantcomprises a brush comprising a core and a plurality of resilientbristles extending from the at a first angle, acute to the core, in itslow profile first configuration and extending from the core at anglegreater than the first angle in its large profile second configuration.33. An implant as defined in claim 32 wherein the core defines aninterior.
 34. An implant as defined in claim 32 wherein the bristles aretubular, each defining an interior.
 35. An implant as defined in claim32 wherein the bristles are configured to carry an angiogenic substance.